The goal of this research is to develop the method of micropenetration to measure the fracture toughness of cartilage in mice and larger species, and then use the method to test a hypothesis on the etiology of osteoarthritis (OA) in a mouse model of OA. Theoretical and experimental methods developed in preliminary work will be refined and used to predict depth of penetration and fracture toughness in bovine cartilage. To validate the method, predicted depth will be compared to that measured by histology; the predicted fracture toughness will be compared with fracture toughness measured using an independent macroscopic method. The sensitivity of predicted fracture toughness to changes in material properties will then be assessed on bovine cartilage subjected to digestion with collagenase. A large deformation, viscoelastic finite element model previously developed will be extended to aid in understanding the process and provide an alternative method for data reduction. After developing the method on I bovine cartilage, the procedures will be transferred to mouse cartilage. For validation, predicted depth of penetration in the mouse will again be compared with that measured by histology. After completing development of the methods in mice, they will be used to measure the fracture toughness in STR/ort mice, a strain that develops premature OA, and CBA mice, a strain that does not develop premature OA, at various ages. Histology and SEM of the mouse cartilage will be used Ito evaluate fibrillation. Data will be used to test the hypothesis that cartilage weakening precedes fibrillation in an animal model of naturally occurring OA.